Optimization of paclitaxel loaded poly (ε-caprolactone) nanoparticles using Box Behnken design

Optimization is a critical process in the development of nanoparticles to apprehend the formulation variables and quality attributes. The purpose of this study was to evaluate the influence of formulation variables viz., drug/polymer ratio (A), surfactant concentration (B) and ratio of volume of internal to external phase (C) on the dependent variables (particle size, % EE and zeta potential) of paclitaxel loaded poly (ε-caprolactone) nanoparticles using Box-Behnken design. The nanoparticles were fabricated using emulsion-solvent evaporation technique. The generated polynomial equations, contour plots and response surface plots of the design space were used to analyze the relationship between independent variables and the observed response. An optimal batch was formulated with selected variables (A: +1 level, B: 0 level, C: −1 level) and the prepared nanoparticles were found to have particle size 215.6 µm, zeta potential −7.52 mV and % drug entrapment 86.78%. The observed responses are in close agreement with the predicted values. NPs were spherical with a smooth surface as revealed by morphological studies and the drug-polymer compatibility was established using FTIR and thermal analysis. The drug was released from the NPs in a biphasic pattern with an initial burst release (32.1 %) followed by sustained release (53 %) at the end of 5 d. The in vitro cell cytotoxicity studies on MCF-7 cells showed that the NPs held superior tumor inhibition ability. The results encourage the application of Box-Behnken design for the optimization of critical variables and fabrication of nanoparticles with desirable properties for drug delivery.